VCV000184016.27 - ClinVar

NM_000455.5(STK11):c.621C>T (p.Asp207=)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(10)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000455.5(STK11):c.621C>T (p.Asp207=)

Variation ID: 184016 Accession: VCV000184016.27

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19p13.3 19: 1220604 (GRCh38) [ NCBI UCSC ] 19: 1220603 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 1, 2016	Oct 8, 2024	Dec 19, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000455.5:c.621C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000446.1:p.Asp207=	synonymous
NC_000019.10:g.1220604C>T
NC_000019.9:g.1220603C>T
NG_007460.2:g.36198C>T
LRG_319:g.36198C>T
LRG_319t1:c.621C>T	LRG_319p1:p.Asp207=

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000019.10:1220603:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00040 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00002

Exome Aggregation Consortium (ExAC) 0.00006

1000 Genomes Project 0.00040

1000 Genomes Project 30x 0.00047

Links

ClinGen: CA023174 dbSNP: rs569380138 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
STK11		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2394	2672

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Hereditary cancer-predisposing syndrome	Likely benign (2)	criteria provided, multiple submitters, no conflicts	Aug 10, 2017	RCV000163122.14
Peutz-Jeghers syndrome	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Dec 19, 2023	RCV000230661.25
not provided	Likely benign (2)	criteria provided, multiple submitters, no conflicts	Sep 13, 2021	RCV000759356.15
Malignant tumor of breast	Likely benign (1)	no assertion criteria provided	-	RCV001356654.9
STK11-related disorder	Likely benign (1)	no assertion criteria provided	Feb 7, 2024	RCV003982911.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Apr 13, 2023)	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023)) Method: clinical testing	Peutz-Jeghers syndrome Affected status: unknown Allele origin: unknown	Myriad Genetics, Inc. Accession: SCV004017966.1 First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023	Comment: This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Likely benign (Aug 30, 2017)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV000888642.2 First in ClinVar: Mar 14, 2019 Last updated: Jan 03, 2022
Likely benign (Aug 10, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000691531.2 First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022
Likely benign (Oct 05, 2016)	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015)) Method: clinical testing	Peutz-Jeghers syndrome Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000489440.2 First in ClinVar: Jul 01, 2016 Last updated: Dec 24, 2022
Likely benign (Sep 13, 2021)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000729206.3 First in ClinVar: Apr 09, 2018 Last updated: Mar 04, 2023
Likely benign (Dec 19, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Peutz-Jeghers syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000284871.10 First in ClinVar: Jul 01, 2016 Last updated: Feb 14, 2024
Likely Benign (Jun 08, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Peutz-Jeghers syndrome (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	All of Us Research Program, National Institutes of Health Accession: SCV004816393.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 Comment: This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more) This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)	Number of individuals with the variant: 2
Likely benign (Oct 22, 2014)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000213634.7 First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024	Comment: This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more) This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Likely benign (Feb 07, 2024)	no assertion criteria provided Method: clinical testing	STK11-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004800597.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Likely benign (-)	no assertion criteria provided Method: clinical testing	Malignant tumor of breast Affected status: yes Allele origin: unknown	Department of Pathology and Laboratory Medicine, Sinai Health System Additional submitter: Franklin by Genoox Study: The Canadian Open Genetics Repository (COGR) Accession: SCV001551884.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021	Comment: The STK11 p.Asp207= variant was not identified in the literature nor was it identified in the LOVD 3.0, Zhejiang Colon Cancer Database, Insight Hereditary Tumors … (more) The STK11 p.Asp207= variant was not identified in the literature nor was it identified in the LOVD 3.0, Zhejiang Colon Cancer Database, Insight Hereditary Tumors Database, databases. The variant was identified in dbSNP (ID: rs569380138) as With Likely benign allele, ClinVar (classified as likely benign by Ambry Genetics, Invitae, Counsyl), Clinvitae (classified as likely benign by ClinVar, Invitae), databases. The variant was identified in control databases in 3 of 210004 chromosomes at a frequency of 0.000014 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include Latino in 1 of 30480 chromosomes (freq: 0.000033), EuropeanNon-Finnish in 1 of 92130 chromosomes (freq: 0.000011), EastAsian in 1 of 15104 chromosomes (freq: 0.000066), while the variant was not observed in the African, Other, AshkenaziJewish, EuropeanFinnish, and SouthAsian populations. The p.Asp207= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. (less)

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Comment:

The STK11 p.Asp207= variant was not identified in the literature nor was it identified in the LOVD 3.0, Zhejiang Colon Cancer Database, Insight Hereditary Tumors Database, databases. The variant was identified in dbSNP (ID: rs569380138) as With Likely benign allele, ClinVar (classified as likely benign by Ambry Genetics, Invitae, Counsyl), Clinvitae (classified as likely benign by ClinVar, Invitae), databases. The variant was identified in control databases in 3 of 210004 chromosomes at a frequency of 0.000014 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include Latino in 1 of 30480 chromosomes (freq: 0.000033), EuropeanNon-Finnish in 1 of 92130 chromosomes (freq: 0.000011), EastAsian in 1 of 15104 chromosomes (freq: 0.000066), while the variant was not observed in the African, Other, AshkenaziJewish, EuropeanFinnish, and SouthAsian populations. The p.Asp207= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs569380138 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_000455.5(STK11):c.621C>T (p.Asp207=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs569380138 ...